Angiogenesis is a process by which new capillary blood vessels are formed. This process occurs normally, e.g., during ovulation and formation of the placenta. It also occurs pathologically in wound healing, as well as in a variety of diseases where uncontrolled or rampant capillary growth is the cause of extensive tissue damage. Examples of the latter are in ophthalmology: diabetic retinopathy, retrolental fibroplasia, corneal graft neovascularization, neovascular glaucoma, ocular tumors and trachoma, where neovascularization may lead to blindness; in dermatology: psoriasis and pyogenic granuloma; in pediatrics: hemangioma, angiofibroma, and hemophiliac joints; in surgery: hypertrophic scars, wound granulation and vascular adhesions; in internal medicine: rheumatoid arthritis, where new vessels in the joint may destroy articular cartilage and scleroderma; in cardiology: atherosclerotic plaque; and in cancer: many kinds of carcinomas and sarcomas, where progressive growth is dependent upon the continuous induction of angiogenesis by these tumor cells.
The realization that tumors, as well as many non-neoplastic diseases, are angiogenesis-dependent has led to a search for angiogenesis inhibitors that might be used therapeutically (See e.g., J. Folkman; Advances in Cancer Research Vol. 43, pp 175-203, 1985 ed. George Klein and Sidney Weinhouse).
Fumagillin is a known compound which has been used as an antimicrobial and antiprotozoal. Its physicochemical properties and method of production are well documented [Production; U.S. Pat. No. 2,803,586: Structure; Proc. Nat. Acad. Sci. USA, 48, 733-735 (1962)].
Fumagillin has a molecular formula of C.sub.26 H.sub.34 O.sub.7. Its molecular weight is 458.53. Yellow needles from methanol extraction have an mp of about 194.degree.-195.degree. C. Fumagillin has the following structure: ##STR1##